scholarly journals Effects of Tumor Necrosis Factor-a on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy

Nephron Extra ◽  
2015 ◽  
Vol 5 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Choon Hee Chung ◽  
Jingyi Fan ◽  
Eun Young Lee ◽  
Jeong Suk Kang ◽  
Seung Joo Lee ◽  
...  
Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 857-865 ◽  
Author(s):  
Matthias Goebeler ◽  
Karin Kilian ◽  
Reinhard Gillitzer ◽  
Manfred Kunz ◽  
Teizo Yoshimura ◽  
...  

Abstract Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C subfamily of chemokines, is important for the local recruitment of leukocytes to sites of inflammatory challenge. Here, we investigated endothelial signaling pathways involving members of the mitogen-activated protein (MAP) kinase superfamily and studied their role for MCP-1 expression in endothelium. We show that tumor necrosis factor- (TNF-), a potent inflammatory activator of endothelium, leads to activation of MAP kinases ERK, p38, and JNK in human umbilical vein endothelial cells (HUVEC). Contribution of MAP kinase pathways to TNF-–induced synthesis of endothelial MCP-1 was then studied by pharmacologic inhibition and transient expression of dominant negative or constitutively active kinase mutants using flow cytometry, Northern blot, and luciferase reporter gene assays. Inhibition of Raf/MEK/ERK or SEK/JNK pathways had no significant effect on MCP-1 levels, whereas blocking the MKK6/p38 pathway by p38 inhibitors SB203580 or SB202190 or by a dominant negative mutant of MKK6, the upstream activator of p38, strongly inhibited TNF-–induced expression of MCP-1. Consistent with that finding, expression of wild-type or constitutively active MKK6 significantly enhanced the effect of limiting TNF- concentrations on MCP-1 synthesis. These data suggest a crucial role for the MKK6/p38 stress kinase cascade in TNF-–mediated endothelial MCP-1 expression.


Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 857-865 ◽  
Author(s):  
Matthias Goebeler ◽  
Karin Kilian ◽  
Reinhard Gillitzer ◽  
Manfred Kunz ◽  
Teizo Yoshimura ◽  
...  

Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C subfamily of chemokines, is important for the local recruitment of leukocytes to sites of inflammatory challenge. Here, we investigated endothelial signaling pathways involving members of the mitogen-activated protein (MAP) kinase superfamily and studied their role for MCP-1 expression in endothelium. We show that tumor necrosis factor- (TNF-), a potent inflammatory activator of endothelium, leads to activation of MAP kinases ERK, p38, and JNK in human umbilical vein endothelial cells (HUVEC). Contribution of MAP kinase pathways to TNF-–induced synthesis of endothelial MCP-1 was then studied by pharmacologic inhibition and transient expression of dominant negative or constitutively active kinase mutants using flow cytometry, Northern blot, and luciferase reporter gene assays. Inhibition of Raf/MEK/ERK or SEK/JNK pathways had no significant effect on MCP-1 levels, whereas blocking the MKK6/p38 pathway by p38 inhibitors SB203580 or SB202190 or by a dominant negative mutant of MKK6, the upstream activator of p38, strongly inhibited TNF-–induced expression of MCP-1. Consistent with that finding, expression of wild-type or constitutively active MKK6 significantly enhanced the effect of limiting TNF- concentrations on MCP-1 synthesis. These data suggest a crucial role for the MKK6/p38 stress kinase cascade in TNF-–mediated endothelial MCP-1 expression.


2003 ◽  
Vol 71 (12) ◽  
pp. 7223-7227 ◽  
Author(s):  
Joram J. Buza ◽  
Yasuyuki Mori ◽  
Abusaleh M. Bari ◽  
Hirokazu Hikono Aodon-geril ◽  
Sachiyo Hirayama ◽  
...  

ABSTRACT Blood from cattle with subclinical Mycobacterium avium subsp. paratuberculosis infection was stimulated with M. avium subsp. paratuberculosis antigens, and expression of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), RANTES, monocyte chemoattractant protein 1 (MCP-1), and IL-8 was measured. Expression of TNF-α, RANTES, and MCP-1 was lower in infected than in uninfected cattle. The reduced response may weaken protective immunity and perpetuate infection.


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